Jonas W. Brinck

• Karolinska Institutet

Background Familial hypercholesterolemia (FH) is a hereditary dyslipidemia that confers a severely elevated risk for development of early atherosclerotic cardiovascular disease if left untreated. FH is underdiagnosed in most countries including Sweden. Aim To develop and evaluate the implementation of a digiphysical screening model to diagnose FH...

Background and Aims Non–HDL-C provides an estimate of lipid-associated risk and is a secondary treatment target after myocardial infarction (MI). The aim was to study the relationship between non–HDL-C levels after MI and risk of adverse outcomes. Methods From the SWEDEHEART registry, 56 262 patients with MI were included. Outcomes were major adve...

The mechanisms underlying endothelial dysfunction in type 1 and type 2 diabetes (T1DM and T2DM) are unresolved. The red blood cells (RBCs) with increased arginase activity induce endothelial dysfunction in T2DM, but the implications of RBCs and the role of arginase inhibition in T1DM are unexplored. We aimed to investigate the differences in endoth...

Aims Hypertriglyceridaemia (hTG) is associated with atherosclerotic cardiovascular disease, pancreatitis, and non-alcoholic fatty liver disease (NAFLD) in large population-based studies. The understanding of the impact of hereditary hTG and cardiometabolic disease status on the development of hTG and its associated cardiometabolic outcomes is more...

Background/Introduction Remote ischemic conditioning (RIC) is the action of brief periods of ischemia to a remote tissue and has been suggested to protect against myocardial ischemia-reperfusion (IR) injury. The outcomes of clinical trials in terms of clinical endpoints and infarct size reduction have been variable, which may be related to influenc...

Aims To investigate plasma lipoprotein(a) [Lp(a)] levels measured in routine clinical care and their association with mortality and cardiovascular disease. Methods and results This retrospective registry-based observational cohort study includes all individuals with plasma Lp(a) results measured at the Karolinska University Laboratory 2003–17. Out...

We have previously shown increased vascular reactivity to angiotensin (Ang) II in familial combined hyperlipidemia. However, this has not been well studied in familial hypercholesterolemia (FH), a condition with incipient endothelial dysfunction. This study aimed to examine microvascular and macrovascular responses to Ang II in FH. Therefore, we in...

Background Nephrotic syndrome causes severe hypercholesterolaemia due to increased production and altered clearance of lipoproteins from the liver. It is challenging for patients with nephrotic syndrome and coronary heart disease to meet LDL-cholesterol (LDL-C) goals for secondary prevention with conventional lipid-lowering therapy. Case summary W...

Background and aims: In familial hypercholesterolemia (FH), statin treatment should be considered from 8-10 years of age, but the prevalence of statin use among children is not known. Methods: Statin use (2008-2018) among children aged 10-14 and 15-19 years old was obtained from the national prescription databases in Norway, Sweden and Denmark. W...

Background Homozygous familial hypercholesterolaemia (FH) is an autosomal-dominant inherited disease presenting with highly elevated low-density lipoprotein cholesterol (LDL-C) levels. Untreated, the patient can develop atherosclerosis and cardiovascular disease already in adolescence. Treatment with statins and ezetimibe is usually not sufficient...

Objective: To investigate the association of the cardiovascular risk factor Lipoprotein(a) [Lp (a)] and vascular complications in patients with type 1 diabetes mellitus. Research design and methods: Patients with type 1 diabetes mellitus receiving regular care were recruited in this observational cross-sectional study and divided into four group...

Background Lipoprotein(a) [Lp(a)] is a cardiovascular risk factor that has been shown to correlate to cardiovascular disease and aortic valve disease. Plasma levels of Lp(a) has a skewed distribution, is highly influenced by genetic inheritance and is not considered to be affected by age, sex or lifestyle. Its importance for the development of vasc...

At the turn of the year 2018/19, a new ICD-10 code (E78.0A) will be introduced in Sweden for the hereditary blood lipid disorder familial hypercholesterolemia (FH). Patients with FH have a significantly increased risk of developing atherosclerotic disease, such as myocardial infarction before the age of 50. However, early diagnosis and start of tre...

Background: Chronic kidney disease (CKD) exacerbates the risk of death due to cardiovascular disease (CVD). Modifications to blood lipid metabolism which manifest as increases in circulating triglycerides and reductions of high density lipoprotein (HDL)-cholesterol are thought to contribute to increased risk. In CKD patients, higher HDL-cholestero...

Background: Patients with heterozygous familial hypercholesterolemia (FH) suffer from high plasma cholesterol and an environment of increased oxidative stress. We examined its potential effects on high density lipoprotein (HDL) associated sphingosine-1-phosphate (S1P) content (HDL-S1P) and HDL-mediated protection against oxidative stress, both wit...

Objective: The dyslipidemia of type 2 diabetes mellitus has multiple etiologies and impairs lipoprotein functionality, thereby increasing risk for cardiovascular disease. High-density lipoproteins (HDLs) have several beneficial effects, notably protecting the heart from myocardial ischemia. We hypothesized that glycation of HDL could compromise th...

We examined potential prothrombotic and proinflammatory effects of angiotensin II in 16 otherwise healthy familial hypercholesterolaemia subjects and 16 matched controls. Markers of fibrinolysis, thrombin generation and inflammation were assessed in plasma before, during and 1h after a 3h intravenous infusion of angiotensin II. In addition, placebo...

New evidence shows that high density lipoproteins (HDL) have protective effects beyond their role in reverse cholesterol transport. Reconstituted HDL (rHDL) offer an attractive means of clinically exploiting these novel effects including cardioprotection against ischemia reperfusion injury (IRI). However, basic rHDL composition is limited to apolip...

Purpose: High-density lipoproteins (HDL) are atheroprotective. New evidence shows that HDL has widespread actions, including protection against cardiac ischemia reperfusion injury (IRI). This cardioprotective role has been attributed to several constituents of the HDL particle, including apolipoprotein A1 (apoA1) the major protein constituent and s...

Abstract We determined the efficacy of a back muscle extensor strengthening program on the back muscle extensor strength, kyphosis, height and thoracic expansion in women with at least one vertebral fracture, kyphosis and osteoporosis. Thirty-six patients were included and randomized to a control or a training group. The training focused on back mu...

The purpose of this study was to explore whether mechanical loading by exercise over a 1-year period in postmenopausal women had an effect on the receptor activator for nuclear factor kappa B ligand/osteoprotegerin (RANKL/OPG) system or the levels of the Wnt-signaling antagonist sclerostin. A total of 112 postmenopausal were randomized to either se...

To examine if healthy borderline overweight postmenopausal women with osteoporosis can improve their waist circumference and lipid profile with a moderate physical training program. Randomized controlled trial. One hundred and twelve postmenopausal women were randomized to normal sedentary life or one year of physical training consisting of three b...

The aim of this study was to investigate whether moderate physical training can improve the bone mineral density (BMD) in women with idiopathic osteoporosis. Ten pre-menopausal women aged 24-44 years diagnosed with idiopathic osteoporosis were included in the study. The physical training program consisted of three fast 30-min walks plus one or two...

One hundred and twelve postmenopausal women with low bone mineral density (BMD) and forearm fractures were randomized to physical training or control group. After one year the total hip BMD was significantly higher in the women in the physical training group. The results indicate a positive effect of physical training on BMD in postmenopausal women...

In the present study we have investigated the expression of mRNAs for hyaluronan synthase isoforms (HAS1, HAS2 and HAS3) in different cells in response to various stimuli. Human mesothelial cells, which synthesize large amounts of hyaluronan, express mRNAs encoding all three HAS isoforms, whereas their transformed counterparts, mesothelioma cells,...

In the present study we investigated the functional properties of the three recombinant hyaluronan synthases (HAS proteins) HAS1, HAS2, and HAS3. HAS3-transfected CHO clones exhibited the highest hyaluronan polymerization rate followed by HAS2 transfectants which were more catalytically active than HAS1 transfectants. In living cells all three HAS...

In the present study we describe a method to prepare membranes with high hyaluronan synthase activity from human glioma cells by pretreatment of the cells with both testicular hyaluronidase and 4-phorbol 12-myristate 13-acetate (PMA). A 23-fold increase in hyaluronan synthase activity was detected in comparison to untreated cells. Using isolated me...